Acidity constants from DFT-based molecular dynamics simulations

In this contribution we review our recently developed method for the calculation of acidity constants from density functional theory based molecular dynamics simulations. The method is based on a half reaction scheme in which protons are formally transferred from solution to the gas phase. The corresponding deprotonation free energies are computed from the vertical energy gaps for insertion or removal of protons. Combined to full proton transfer reactions, the deprotonation energies can be used to estimate relative acidity constants and also the Brønsted pK(a) when the deprotonation free energy of a hydronium ion is used as a reference. We verified the method by investigating a series of organic and inorganic acids and bases spanning a wide range of pK(a) values (20 units). The thermochemical corrections for the biasing potentials assisting and directing the insertion are discussed in some detail.